On the top of ARB N/L type Ca channel blocker leads to less elevation of aldosterone

Synopsis The activation of the renin-angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one. Subjects were 60 hypertensives administered with valsartan. As an open label study, amlodipine (L type) or cilnidipine (N/L type) were administered on the top of valsartan (ARB) in a cross-over manner. Results were as follows (valsartan + amlodipine compared with valsartan + cilnidipine): systolic blood pressure (SBP)/diastolic blood pressure (DBP) (mmHg): 132 + − 10/76 + − 10 compared with 131 + − 10/77 + − 9, P = 0.95/0.48, plasma renin activity (PRA) (ng/ml·h): 2.41 + − 2.67 compared with 2.00 + − 1.50 P = 0.20, PAC (pg/ml): 77.3 + − 31.0 compared with 67.4 + − 24.8, P < 0.05, urinary albumin excretion (UAE) (mg/gCr): 105.9 + − 216.1 compared with 73.9 + − 122.2, P < 0.05. Thus, PAC at cilnidipine was significantly lower than those at amlodipine in spite of the comparable BP reductions. Besides, UAE was significantly lower at cilnidipine. In conclusion, on the top of the ARB, it is suggested that cilnidipine administration might lead to less elevation of PAC and reduction in UAE compared with amlodipine

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

AbstractThe VLDL receptor, a newly identified lipoprotein receptor, recognizes apoE containing lipoproteins. The human VLDL receptor was overexpressed in ldlA-7, a mutant Chinese hamster ovary cells lacking LDL receptors. Each VLDL obtained from a normolipidemic subject with two ε3 or ε2 alleles similarly competed for the binding of radiolabeled rabbit β-VLDL to the VLDL receptors. The anti-apoE monoclonal antibody 1D7, which inhibited binding of apoE3 to the LDL receptors, failed to compete for the binding of VLDL (apoE3 or apoE2) to the VLDL receptors. Results indicate that the binding site of apoE on the VLDL receptor may differ from its binding site on the LDL receptor